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Endometriosis and susceptibility to multiple sclerosis: is there any absolute truth?

European Journal of Obstetrics & Gynecology and Reproductive Biology, Volume 179, August 2014, Page 253

Dear Editor,

We suppose that women suffering from endometriosis may have an increased risk of developing multiple sclerosis (MS). We think that these conditions may share common humoral immune abnormalities in accordance with the characteristics of autoimmune diseases. Endometriosis is a complex condition defined by the growth of vascularized endometrial tissue in extrauterine sites, typically the pelvis, with pain and infertility [1]. Immunologic mechanisms have been proposed to contribute to the pathophysiology of endometriosis, implying an inflammatory behavior [1], [2], and [3]. Macrophages have been shown to play a pivotal role in the onset and progression of endometriosis [1] and [2]. It has been suggested that endometriosis may be due to a misperception of macrophages about ectopic endometrial tissue [1]. Macrophages seem to perceive endometriotic cells as a wound and activate programs leading to ectopic cell survival and tissue vascularization [1]. Macrophages are activated by interferon-γ (IFN-γ) that is a pro-inflammatory cytokine considered as the classic macrophage-activating factor [1]. Interestingly, endometriosis has been linked to TH1/TH2 imbalance with a dominance of pro-inflammatory TH1 profile over TH2 anti-inflammatory response similarly to typical autoimmune diseases [2]. Among TH1 cytokines, IFN-γ has been demonstrated to have a major role in the pathogenesis of endometriosis [1] and [2]. In light of the evidence of underlying immune dysregulation, it has been speculated a possible relationship between endometriosis and other immune-mediated disorders [3]. In this contest, it has been reported that women with endometriosis may be more likely to be diagnosed with MS than healthy controls [3]. However, not all studies have found a consistent link between endometriosis and MS [3]. What is more, the molecular basis for the association of endometriosis with MS has not been proved until now [3]. MS is a chronic inflammatory, demyelinating disorder of the central nervous system (CNS) [4]. It is the most common cause of neurological disability among young adults [4]. Similarly to endometriosis, macrophages have been found to be directly involved in the pathogenesis of MS [4] and [5]. Macrophages are the most predominant immune cell type in inflammatory demyelinating MS lesions [4]. However, it has been detected that macrophages may play a dual role of exerting neuroprotective and growth promoting effects but also contributing to tissue damage by production of inflammatory mediators [4]. Intriguingly, the balance between TH1 and TH2 related cytokines has also been revealed to play a crucial role in lesion formation and axonal damage [5]. In particular, a predominant TH1 immune profile has been associated with the disease process [4] and [5]. Among the increased Th1 cytokines, IFN-γ has been strongly connected with the pathomechanisms of MS [4] and [5]. Interestingly, the activation status of macrophages in MS lesions has been related to stimulation with IFN-γ [4]. Concordantly, it has been reported that IFN-γ levels correlate with disease progression and worsening of symptoms [5]. Considering these observations, we hypothesize that the co-occurrence of endometriosis with MS may be a true association. Although MS and endometriosis are clearly different in their phenotype, they seem to be characterized by a common autoimmune background resulting both in the establishment of endometriosis and in the possible increased risk of women with endometriosis to develop MS. A feature common to these diseases is the macrophage priming with enhanced production of IFN-γ linked to a higher Th1 activity. We propose that patients with endometriosis should be monitored closely to ensure early detection of MS. Moreover, it would be advisable to consider the coexistence of other co-morbid autoimmune disorders in women with endometriosis. Research studies are needed to open up possibilities for the implementation of new strategies for immunomodulatory intervention therapy promoting a shift toward the anti-inflammatory TH2 profile response over the dominating Th1 system in order to halt or even prevent both endometriosis and MS.

References

  • [1] A. Capobianco, P. Rovere-Querini. Endometriosis, a disease of the macrophages. Front Immunol. 2013;4:9
  • [2] S. Podgaec, J.A. Dias Junior, C. Chapron, et al. TH1 and TH2 immune responses related to pelvic endometriosis. Rev Assoc Med Bras. 2010;56:92-98 Crossref
  • [3] N.M. Nielsen, K.T. Jorgensen, B.V. Pedersen, K. Rostgaard, M. Frisch. The co-occurrence of endometriosis with multiple sclerosis, systemic lupus erythematosus and Sjogren syndrome. Hum Reprod. 2011;26(6):1555-1559 Crossref
  • [4] D.Y.S. Vogel, E.J.F. Vereyken, J.E. Glim, et al. Macrophages in inflammatory multiple sclerosis lesions have an intermediate activation status. J Neuroinflammation. 2013;10:35 Crossref
  • [5] C. Oreja-Guevara, J. Ramos-Cejudo, L. Stark Aroeira, B. Chamorro, E. Diez-Tejedor. TH1/TH2 Cytokine profile in relapsing-remitting multiple sclerosis patients treated with glatiramer acetate or natalizumab. BMC Neurol. 2012;12:95 Crossref

Footnotes

a Division of Pediatrics and Neonatology, Moscati Hospital, Via A. Gramsci 3, 81031 Aversa, Italy

b Division of Gynecology, San Carlo di Nancy Hospital, Rome, Italy

Corresponding author. Tel.: +39 3392045468.

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About the Editors

  • Prof Timothy Vartanian

    Timothy Vartanian, Professor at the Brain and Mind Research Institute and the Department of Neurology, Weill Cornell Medical College, Cornell...
  • Dr Claire S. Riley

    Claire S. Riley, MD is an assistant attending neurologist and assistant professor of neurology in the Neurological Institute, Columbia University,...
  • Dr Rebecca Farber

    Rebecca Farber, MD is an attending neurologist and assistant professor of neurology at the Neurological Institute, Columbia University, in New...

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